Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis.

BACKGROUND: A previous individual patient data meta-analysis by the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) collaborative group to assess the addition of chemotherapy to radiotherapy showed that it improves overall survival in nasopharyngeal carcinoma. This benefit was restricted to patients receiving concomitant chemotherapy and radiotherapy. The aim of this study was to update the meta-analysis, include recent trials, and to analyse separately the benefit of concomitant plus adjuvant chemotherapy. METHODS: We searched PubMed, Web of Science, Cochrane Controlled Trials meta-register, ClinicalTrials.gov, and meeting proceedings to identify published or unpublished randomised trials assessing radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma and obtained updated data for previously analysed studies. The primary endpoint of interest was overall survival. All trial results were combined and analysed using a fixed-effects model. The statistical analysis plan was pre-specified in a protocol. All data were analysed on an intention-to-treat basis. FINDINGS: We analysed data from 19 trials and 4806 patients. Median follow-up was 7·7 years (IQR 6·2-11·9). We found that the addition of chemotherapy to radiotherapy significantly improved overall survival (hazard ratio [HR] 0·79, 95% CI 0·73-0·86, p<0·0001; absolute benefit at 5 years 6·3%, 95% CI 3·5-9·1). The interaction between treatment effect (benefit of chemotherapy) on overall survival and the timing of chemotherapy was significant (p=0·01) in favour of concomitant plus adjuvant chemotherapy (HR 0·65, 0·56-0·76) and concomitant without adjuvant chemotherapy (0·80, 0·70-0·93) but not adjuvant chemotherapy alone (0·87, 0·68-1·12) or induction chemotherapy alone (0·96, 0·80-1·16). The benefit of the addition of chemotherapy was consistent for all endpoints analysed (all p<0·0001): progression-free survival (HR 0·75, 95% CI 0·69-0·81), locoregional control (0·73, 0·64-0·83), distant control (0·67, 0·59-0·75), and cancer mortality (0·76, 0·69-0·84). INTERPRETATION: Our results confirm that the addition of concomitant chemotherapy to radiotherapy significantly improves survival in patients with locoregionally advanced nasopharyngeal carcinoma. To our knowledge, this is the first analysis that examines the effect of concomitant chemotherapy with and without adjuvant chemotherapy as distinct groups. Further studies on the specific benefits of adjuvant chemotherapy after concomitant chemoradiotherapy are needed. FUNDING: French Ministry of Health (Programme d'actions intégrées de recherche VADS), Ligue Nationale Contre le Cancer, and Sanofi-Aventis.

Plants of the Annonaceae traditionally used as antimalarials: a review

Species of the Annonaceae family are used all over the tropics in traditional medicine in tropical regions for the treatment of malaria and other illnesses. Phytochemical studies of this family have revealed chemical components which could offer new alternatives for the treatment and control of malaria. Searches in scientific reference sites (SciFinder Scholar, Scielo, PubMed, ScienceDirect and ISI Web of Science) and a bibliographic literature search for species of Annonaceae used traditionally to treat malaria and fever were carried out. This family contains 2,100 species in 123 genera. We encountered 113 articles reporting medicinal use of one or more species of this family including 63 species in 27 genera with uses as antimalarials and febrifuges. Even though the same species of Annonaceae are used by diverse ethnic groups, different plant parts are often chosen for applications, and diverse methods of preparation and treatment are used. The ethanol extracts of Polyalthia debilis and Xylopia aromatica proved to be quite active against Plasmodium falciparum in vitro (median inhibition concentration, IC50 < 1.5 µg/mL). Intraperitoneal injection of Annickia chlorantha aqueous extracts (cited as Enantia chlorantha) cleared chloroquine-resistant Plasmodium yoelii nigeriensis from the blood of mice in a dose-dependant manner. More phytochemical profiles of Annonaceous species are required; especially information on the more commonly distributed antimalarial compounds in this family.

Effects of Three Types of Exercise Interventions on Healthy Old Adults' Gait Speed : A Systematic Review and Meta-Analysis.

BACKGROUND: Habitual walking speed predicts many clinical conditions later in life, but it declines with age. However, which particular exercise intervention can minimize the age-related gait speed loss is unclear. PURPOSE: Our objective was to determine the effects of strength, power, coordination, and multimodal exercise training on healthy old adults' habitual and fast gait speed. METHODS: We performed a computerized systematic literature search in PubMed and Web of Knowledge from January 1984 up to December 2014. Search terms included 'Resistance training', 'power training', 'coordination training', 'multimodal training', and 'gait speed (outcome term). Inclusion criteria were articles available in full text, publication period over past 30 years, human species, journal articles, clinical trials, randomized controlled trials, English as publication language, and subject age ≥65 years. The methodological quality of all eligible intervention studies was assessed using the Physiotherapy Evidence Database (PEDro) scale. We computed weighted average standardized mean differences of the intervention-induced adaptations in gait speed using a random-effects model and tested for overall and individual intervention effects relative to no-exercise controls. RESULTS: A total of 42 studies (mean PEDro score of 5.0 ± 1.2) were included in the analyses (2495 healthy old adults; age 74.2 years [64.4-82.7]; body mass 69.9 ± 4.9 kg, height 1.64 ± 0.05 m, body mass index 26.4 ± 1.9 kg/m(2), and gait speed 1.22 ± 0.18 m/s). The search identified only one power training study, therefore the subsequent analyses focused only on the effects of resistance, coordination, and multimodal training on gait speed. The three types of intervention improved gait speed in the three experimental groups combined (n = 1297) by 0.10 m/s (±0.12) or 8.4 % (±9.7), with a large effect size (ES) of 0.84. Resistance (24 studies; n = 613; 0.11 m/s; 9.3 %; ES: 0.84), coordination (eight studies, n = 198; 0.09 m/s; 7.6 %; ES: 0.76), and multimodal training (19 studies; n = 486; 0.09 m/s; 8.4 %, ES: 0.86) increased gait speed statistically and similarly. CONCLUSIONS: Commonly used exercise interventions can functionally and clinically increase habitual and fast gait speed and help slow the loss of gait speed or delay its onset.

A rationalist perspective on the autonomy of international sport governing bodies : towards a pragmatic autonomy in the steering of sports

International sport governing bodies (ISGBs) are built on the foundations of freedom of association and traditionally enjoy a large degree of autonomy in their decision-making. Their autonomy is increasingly confined, however, and their hierarchical self-governance is giving way to a more networked governance, in which different stakeholders exert power in different ways and in different contexts in a complex web of interrelationships. Taking a rationalist perspective on the autonomy of ISGBs, this article demonstrates that ISGBs are deploying strategies to safeguard their waning governing monopoly over international sport. Opting for an inductive approach, the authors present four possible conceptualizations of autonomy as applied to ISGBs, namely political autonomy, legal autonomy, financial autonomy and pyramidal autonomy. For each dimension, they describe the different strategies ISGBs wield in order to safeguard different dimensions of their autonomy. This article uses governance theories to hypothesize that the autonomy of ISGBs can be understood as 'pragmatic autonomy' since ISGBs only cede certain aspects of their autonomy under particular circumstances and when being subject to specific threats. Acting in a rationalist manner, they are able to keep control over governance developments in sport by using indirect and more subtle forms of governance.

Impact of Aldosterone Antagonists on Sudden Cardiac Death Prevention in Heart Failure and Post-Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVES: Sudden cardiac death (SCD) is a severe burden of modern medicine. Aldosterone antagonist is publicized as effective in reducing mortality in patients with heart failure (HF) or post myocardial infarction (MI). Our study aimed to assess the efficacy of AAs on mortality including SCD, hospitalization admission and several common adverse effects. METHODS: We searched Embase, PubMed, Web of Science, Cochrane library and clinicaltrial.gov for randomized controlled trials (RCTs) assigning AAs in patients with HF or post MI through May 2015. The comparator included standard medication or placebo, or both. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Event rates were compared using a random effects model. Prospective RCTs of AAs with durations of at least 8 weeks were selected if they included at least one of the following outcomes: SCD, all-cause/cardiovascular mortality, all-cause/cardiovascular hospitalization and common side effects (hyperkalemia, renal function degradation and gynecomastia). RESULTS: Data from 19,333 patients enrolled in 25 trials were included. In patients with HF, this treatment significantly reduced the risk of SCD by 19% (RR 0.81; 95% CI, 0.67-0.98; p = 0.03); all-cause mortality by 19% (RR 0.81; 95% CI, 0.74-0.88, p<0.00001) and cardiovascular death by 21% (RR 0.79; 95% CI, 0.70-0.89, p<0.00001). In patients with post-MI, the matching reduced risks were 20% (RR 0.80; 95% CI, 0.66-0.98; p = 0.03), 15% (RR 0.85; 95% CI, 0.76-0.95, p = 0.003) and 17% (RR 0.83; 95% CI, 0.74-0.94, p = 0.003), respectively. Concerning both subgroups, the relative risks respectively decreased by 19% (RR 0.81; 95% CI, 0.71-0.92; p = 0.002) for SCD, 18% (RR 0.82; 95% CI, 0.77-0.88, p < 0.0001) for all-cause mortality and 20% (RR 0.80; 95% CI, 0.74-0.87, p < 0.0001) for cardiovascular mortality in patients treated with AAs. As well, hospitalizations were significantly reduced, while common adverse effects were significantly increased. CONCLUSION: Aldosterone antagonists appear to be effective in reducing SCD and other mortality events, compared with placebo or standard medication in patients with HF and/or after a MI.

Host Genetics of Response to Hepatitis B Vaccine: A Systematic Review

Background. Hepatitis B virus (HBV) is an important cause of chronic viral disease worldwide and can be life threatening. While a safe and effective vaccine is widely available, 5 to 10% of healthy vaccinees fail to achieve a protective anti-hepatitis B surface antigen antibody (anti-HBs) titer (>10mIU/ml). A limited number of studies investigated host genetics of the response to HBV vaccine. To our knowledge, no comprehensive overview of genetic polymorphisms both within and outside the HLA system has been done so far. Aim. The aim of this study was to perform a systematic review of the literature of human genetics influencing immune response after hepatitis B vaccination. Methods. Literature searches using keywords were conducted in the electronic databases Medline, Embase and ISI Web of Science the cut-off date being March 2014. After selection of papers according to stringent inclusion criteria, relevant information was systematically collected from the remaining articles, including demographic data, number of patients, schedule and type of vaccine, phenotypes, genes and single nucleotide polymorphisms (SNPs) genotyping results and their association with immune response to hepatitis B vaccine. Results. The literature search produced a total of 1968 articles from which 46 studies were kept for further analyses. From these studies, data was extracted for 19 alleles from the human leukocyte antigen (HLA) region that were reported as significant at least twice. Among those alleles, 9 were firmly associated with vaccine response outcome (DQ2 [DQB1*02 and DQB1*0201], DR3 [DRB1*03 and DRB1*0301], DR7 [DRB1*07 and DRB1*0701], C4AQ0, DPB1*0401, DQ3, DQB1*06, DRB1*01 and DRB1*13 [DRB1*1301]). In addition, data was extracted for 55 different genes from which 13 extra-HLA genes had polymorphisms that were studied by different group of investigators or by the same group with a replication study. Among the 13 genes allowing comparison, 4 genes (IL-1B, IL-2, IL-4R and IL- 6) revealed no significant data, 6 genes (IL-4, IL-10, IL-12B, IL-13, TNFA, IFNG and TLR2) were explored with inconsistent results and 2 genes (CD3Z and ITGAL) yielded promising results as their association with vaccine response was confirmed by a replication approach. Furthermore, this review produced a list of 46 SNPs from 26 genes that were associated with immune response to vaccine only once, providing novel candidates to be tested in datasets from existing genome-wide association studies (GWAS). Conclusion. To the best of our knowledge, this is the first systematic review of immunogenetic studies of response to hepatitis B vaccine. While this work reassesses the role of several HLA alleles on vaccine response outcome, the associations with polymorphisms in genes outside the HLA region were rather inconsistent. Moreover, this work produced a list of 46 significant SNPs that were reported by a single group of investigators, opening up some interesting possibilities for further research.

Knowledge Map of Research on Biofuels

This work highlights and analyzes the citations and co-citations by different authors, countries and institutions in series of researches on biofuel. These relations represent a knowledge map which shows the areas of research by different countries and authors. The contributions of different institutions were also shown. With this knowledge map developed, areas of research that still need more attention as well as the most important studies were highlighted. The software used for this analysis is Citespace which is developed by Chaomei Chen. Sources of information are articles retrieved from ISI Web of Science. Biofuel as a renewable form of energy is discussed. Its sources, types, methods of production, effects, market, and producers were discussed. Also plans and strategies that aim at boosting world biofuel market were listed as well as recent researches on it. Knowledge mapping, its types and methods as well as the method and software used for the analysis were also discussed.

Limnological research in the Iberian Peninsula: a ten-year survey of published literature.

Research on limnology in southern Europe had achieved a notable presence in the international arena before the onset of the current dramatic cuts in public investment in science. We assessed the limnological research published in peer-reviewed journals by Spanish and Portuguese (i.e., Iberian) researchers during the decade prior to the economic recession (2000 to 2009). The Thompson Reuters Web of Knowledge database was used to retrieve all publications on limnology authored by researchers affiliated with Spanish or Portuguese institutions independently of the geographical setting of the study. The publishing pattern was characterised in terms of authors, journals, and citation statistics. In addition, a thematic characterisation of the research was performed by a manual assignation of several categorical descriptors combined with a blind word count analysis. Iberian researchers produced an annual mean of 278 papers on limnology. Papers were published in journals that had impact factors ranging from 0.1 to 31.4, with a mean of 2.0. Based on citations, the impact of the Iberian limnological research was not due to a few highly cited papers but rather to a wide number of publications; each paper received a mean of 8 citations. The Iberian limnological research involved up to 5460 researchers, with a mean of 4.3 authors per paper. The research largely focused on fluvial systems, with 47 % of total publications (2778) devoted to these ecosystems. There was a dominant focus on local, within-system aspects of study sites and the research was mostly restricted to the Iberian Peninsula; larger spatial scales of analysis (i.e., landscape, regional, or global) tended to be overlooked. Iberian research addressed fundamental (75 %) rather than applied (17 %) or methodological (5 %) questions and was vastly dominated by observational approaches (75 %). Interestingly, Iberian limnological research increased its scientific productivity during the analysed decade at a higher rate than its international counterpart (increase of 119 %). Overall, Iberian research on limnology appeared to be in good health during the analysed decade. Certain areas have been more studied than others, which opens opportunities to develop new research.

Identification of Turning Points in the Research on Titanium Dioxide Production and Application

This dissertation "Identification of turning points in the research on titanium dioxide production and application" aims at detecting in scientific literatures emerging trends and sudden changes in titanium dioxide production and application. These key changes are then studied to determine its transient patterns and its effect on the research on titanium dioxide production and application The source of information is from bibliographic data which discussed titanium dioxide production and application. These bibliographic data where obtained from ISI Web of Knowledge and then formed into a network of clusters by applying software called Citespace.

Neurocognition in schizophrenia: a study of the productivity and visibility of spanish authors

This paper provides a map of the scientific productivity of authors affiliated to a Spanish institution and who have addressed one of the most important current topics in schizophrenia: The study of cognitive performance. A search of the Web of Science yielded 125 articles that met the inclusion criteria. In order to provide a comprehensive overview of scientific productivity, we examine several bibliometric indicators, concerning both productivity and impact or visibility. The analysis also focuses on qualitative aspects of key theoretical importance, such as the kinds of cognitive functions that are most often assessed and the tests most widely used to evaluate them in clinical practice. The study shows that interest in the subject of cognitive function in schizophrenia has increased considerably in Spain since the beginning of this century. The results also highlight the need to standardize the type of tests to be used in the cognitive assessment of patients with schizophrenia.

A importância das revistas Química Nova e Journal of the Brazilian Chemical Society no crescimento da área de química no Brasil

Quimica Nova and the Journal of the Brazilian Chemical Society are two examples of successful initiatives taken by the Brazilian Chemical Society (SBQ - Sociedade Brasileira de Química), and may serve as models for the scientific societies of developing countries. Pillars of the SBQ, these two periodicals are undeniable demonstrations that idealism, utopia and dignity are the essential ingredients for transforming dreams into reality. Few believed that the Brazilian chemical community would one day have, as it does today, two scientific research periodicals indexed in the principal international data banks.

The Art & Science of Learning Design

We live in an era defined by a wealth of open and readily available information, and the accelerated evolution of social, mobile and creative technologies. The provision of knowledge, once a primary role of educators, is now devolved to an immense web of free and readily accessible sources. Consequently, educators need to redefine their role not just ¿from sage on the stage to guide on the side¿ but, as more and more voices insist, as ¿designers for learning¿.The call for such a repositioning of educators is heard from leaders in the field of technology-enhanced learning (TEL) and resonates well with the growing culture of design-based research in Education. However, it is still struggling to find a foothold in educational practice. We contend that the root causes of this discrepancy are the lack of articulation of design practices and methods, along with a shortage of tools and representations to support such practices, a lack of a culture of teacher-as-designer among practitioners, and insufficient theoretical development.The Art and Science of Learning Design (ASLD) explores the frameworks, methods, and tools available for teachers, technologists and researchers interested in designing for learning Learning Design theories arising from findings of research are explored, drawing upon research and practitioner experiences. It then surveys current trends in the practices, methods, and methodologies of Learning Design. Highlighting the translation of theory into practice, this book showcases some of the latest tools that support the learning design process itself.

Research Data Management in the Cloud

Workshop at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Glutamate-N-methyl-D-aspartate receptor modulation and minocycline for the treatment of patients with schizophrenia: an update

Growing consistent evidence indicates that hypofunction of N-methyl-D-aspartate (NMDA) transmission plays a pivotal role in the neuropathophysiology of schizophrenia. Hence, drugs which modulate NMDA neurotransmission are promising approaches to the treatment of schizophrenia. The aim of this article is to review clinical trials with novel compounds acting on the NMDA receptor (NMDA-R). This review also includes a discussion and translation of neuroscience into schizophrenia therapeutics. Although the precise mechanism of action of minocycline in the brain remains unclear, there is evidence that it blocks the neurotoxicity of NMDA antagonists and may exert a differential effect on NMDA signaling pathways. We, therefore, hypothesize that the effects of minocycline on the brain may be partially modulated by the NMDA-R or related mechanisms. Thus, we have included a review of minocycline neuroscience. The search was performed in the PubMed, Web of Science, SciELO, and Lilacs databases. The results of glycine and D-cycloserine trials were conflicting regarding effectiveness on the negative and cognitive symptoms of schizophrenia. D-serine and D-alanine showed a potential effect on negative symptoms and on cognitive deficits. Sarcosine data indicated a considerable improvement as adjunctive therapy. Finally, minocycline add-on treatment appears to be effective on a broad range of psychopathology in patients with schizophrenia. The differential modulation of NMDA-R neurosystems, in particular synaptic versus extrasynaptic NMDA-R activation and specific subtypes of NMDA-R, may be the key mediators of neurogenesis and neuroprotection. Thus, psychotropics modulating NMDA-R neurotransmission may represent future monotherapy or add-on treatment strategies in the treatment of schizophrenia.

Animal models of prenatal immune challenge and their contribution to the study of schizophrenia: a systematic review

Prenatal immune challenge (PIC) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism. Based on this, the goal of this article was to review the main contributions of PIC models, especially the one using the viral-mimetic particle polyriboinosinic-polyribocytidylic acid (poly-I:C), to the understanding of the etiology, biological basis and treatment of schizophrenia. This systematic review consisted of a search of available web databases (PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge) for original studies published in the last 10 years (May 2001 to October 2011) concerning animal models of PIC, focusing on those using poly-I:C. The results showed that the PIC model with poly-I:C is able to mimic the prodrome and both the positive and negative/cognitive dimensions of schizophrenia, depending on the specific gestation time window of the immune challenge. The model resembles the neurobiology and etiology of schizophrenia and has good predictive value. In conclusion, this model is a robust tool for the identification of novel molecular targets during prenatal life, adolescence and adulthood that might contribute to the development of preventive and/or treatment strategies (targeting specific symptoms, i.e., positive or negative/cognitive) for this devastating mental disorder, also presenting biosafety as compared to viral infection models. One limitation of this model is the incapacity to model the full spectrum of immune responses normally induced by viral exposure.